A high proportion of thymocytes from F/St mice produce xenotropic murine leukemia viruses (X-MuLV) but expression of infectious virus is markedly suppressed in all F1 hybrids of F/St with other strains. Suppression of X-MuLV is governed by a single dominant gene which maps within or very close to the H-2 complex. This gene appears to exert a negative regulatory influence on a chromosome 1 X-MuLV induction locus. NFS mice infected with a wild mouse ecotropic MuLV develop splenic lymphomas and hind limb paralysis. Dualtropic MuLV appear in spleen cells but not thymocytes or brain prior to the onset of either disease. The lymphomas appearing in these mice are predominantly erythroleukemias and their development is accelerated by treatment with antithymocyte serum. NFS mice congenic for the AKR ecotropic MuLV loci develop splenic lymphomas between one and two years of age. These tumors, previously classified as reticulum cell sarcoma Type B, have been shown to be neoplasms of B lymphocytes. A dominant gene for resistance of mouse tissues to infection with dualtropic MuLV was mapped to chromosome 5 in close linkage with Hm.